Direct method for prenatal diagnosis and carrier detection in Duchenne/Becker muscular dystrophy using the entire dystrophin cDNA.
Direct method for prenatal diagnosis and carrier detection in Duchenne/Becker muscular dystrophy using the entire dystrophin cDNA.
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使用完整肌营养不良蛋白 cDNA 进行杜氏/贝克型肌营养不良症产前诊断和携带者检测的直接方法。
DOI：
10.1002/ajmg.1320290341
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Francke,U
中科院分区：
文献类型：
--
作者：
Darras,BT;Koenig,M;Kunkel,LM;Francke,U
DNA序列多态性（RFLP）已被广泛用作遗传标记，用于鉴定受影响家族中携带杜氏肌营养不良症（DMD）突变的X染色体，但该方法存在严重的局限性和缺陷[Darras等人，1QP71. DME基因的互补DNA（cDPA）最近已被分离并显示在大比例的OF患者中检测部分基因缺失[Koenig等人，19871.两个产前研究，以说明如何明确识别的缺失突变的cDNA探针允许直接基于DNA的诊断，具有高准确性，否则信息不足的家庭。在一个先证者家族中，DNA标记分析确定了存在于患病男性中的Xp 21染色体区域在随后的妊娠中也被男性胎儿携带。用覆盖整个14 kb cDNA的探针分析该家族的DNA，发现受影响的男性中存在一个小的缺失，该缺失不存在于胎儿或母亲中。第二个家系的胎儿是一个女性缺失携带者，通过比较限制性片段的强度来确定。由于1/3的DMD患者被认为是由新的突变引起的，并且大多数家庭只有单个受影响的男性，因此现在可用的克隆cDNA探针可能会彻底改变这种疾病中基于DNA的诊断研究。更可靠、更快速
DNA sequence polymorphisms (RFLPs) have been widely used as genetic markers for identification of the X chromosome that carries the mutation for Duchenne muscular dystrophy (DMD) in affected families, but serious limitations and pitfalls are associated with this aFproach [Darras et al., 1QP71. The complementary DNA (cDPA) of the DME gene has recently been isolated and shown to detect partial gene deletions in a large proportion OF patients [Koenig et al., 19871. Two prenatal studies are presented to illustrate how the unambiguous identification of deletion mutations by cDNA probes permits direct DNA-based diagnoses with high accuracy and in otherwise uninformative Families. Tn a single proband family, DNA marker analysis had determined that the Xp21 chromosomal region present in the affected male was also carried bv a male fetus in a subsequent pregnancy. Analysis of this family's DNA with probes covering the entire 14 kb cDNA revealed a small deletion in the affected male that was not present in the fetus nor in the mother. In the second family the fetus was a female deletion carrier identified by comparing intensities of restriction fragments. Since 1/3 of all DMD patients are thought to result from new mutations and most families have only single affected males, the cloned cDNA probes now available are likely to revolutionize DNA-based diagnostic studies in this disorder. More reliable, more rapid